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While she started out as a transgender leader—founding the first national transgender advocacy group (GenderPAC) -- her analysis and work broadened over time to include discrimination and violence regardless of individuals' identity. While this perspective has been widely accepted, its breadth has provoked criticism by some in the transgender community. Wilchins' work and writing has often focused on youth, whom she not only sees as uniquely vulnerable to the gender system's pressures and harm, but whom she sees as capable of "looking with fresh eyes." Wilchins' work has been instrumental in bringing transgender rights into the mainstream LGBT movement, and has helped bring awareness of the impact of gender norms to a wider audience. In 2001, Wilchins' work resulted in her being selected one of just six community activists named by TIME Magazine among its "100 Civic Innovators for the 21st Century." A founding member of Camp Trans, since the mid-1990s Wilchins has been highly active in founding a number of organizations and events focused on gender issues, including:

The Transexual Menace, the first large direct action group for transgender rights, which was modeled along the lines of Queer Nation and which at one point boasted representatives in 40+ cities (co-founder Denise Norris).

In 1995 Wilchins founded the Gender Public Advocacy Coalition GenderPAC, a tax-exempt organization focused on gender rights issues. GenderPAC originally focused on the transgender community, but gradually broadened its focus to include anyone who suffered discrimination or violence because of their gender identity or gender expression. GenderPAC described its mission as the creation of "classrooms, communities, and workplaces [that] are safe for everyone to learn, grow, and succeed — whether or not they meet expectations for masculinity and femininity. In late 1999, the organization was incorporated and received tax-exempt status. In 2009 it rebranded and relaunched as a new organization, effectively ceasing operations as GenderPAC.

While GenderPAC's Executive Director,[2] Wilchins helped dozens of corporations as diverse as IBM, JP Morgan Chase, and Citigroup, as well as major funders like the Arcus and Gill Foundations to expand their employment non-discrimination policies to include gender identity and gender expression. GenderPAC's Congressional Non-Discrimination Pledge eventually had almost 200 sponsors, including both Republicans and US Senators. She helped compile and publish the GENIUS (Gender Equality National Index for Universities & Schools) Index, which rated and ranked schools' adoption of gender identity protections. During her watch, GenderPAC also launched the GenderYOUTH Network, which eventually supported student groups at 100+ schools in creating safer and friendlier environments for those who were gender non-conforming on their own campuses.

With help from researcher Emilia Lombardi, GenderPAC compiled and published the "1st National Survey of TransViolence," based on surveys provided by more than 500 respondents. In 2006, GenderPAC researched and published "50 Under 30: Masculinity & the War on America's Youth," the first human rights report to document an under-reported tide of violence that had claimed the lives of more than 50 young people aged 30 and under attacked because of their gender identity or gender expression from 1994-2004. With a fresh round of attacks, the report was reissued just two years later as "70 Under 30." More than 80 groups endorsed the reports' recommendations, including the Leadership Conference on Civil and Human Rights, National Organization for Women (NOW), National Council of La Raza (NCLR), Interfaith Alliance, and the Human Rights Campaign. The report was used by the House Sub-Committee which marked up the Matthew Shepard Hate Crime Act (the final bill included gender identity as a protected category and was eventually passed and signed into law).

The Moderating Effects of Support for Violence Beliefs on Masculine Norms, Aggression, and Homophobic Behavior During Adolescence, Paul Poteat, Michael Kimmel, Riki Wilchins, 2011). Journal of Research on Adolescence, 21, 434-447